A study of the mechanism of replication of the RNA of negative-stranded, single-stranded RNA viruses using vesicular stomatitis virus (VSV) as a prototype will be carried out in cell culture. The study will involve the following specific areas: 1) A characterization of replicative forms and replicative intermediates involved in the replication of VSV RNA. 2) An analysis of the temporal relationship of replicative structures to other forms of VSV RNA. 3) A study of the relationship of protein synthesis to viral RNA synthesis. 4) The characterization of VSV temperature-sensitive RNA mutants. 5) A search for viral specific proteins involved in RNA replication and identification of their function. This study will involve the introduction and evaluation of a new technique for following RNA metabolism in cells in culture. BIBLIOGRAPHIC REFERENCES: Wertz, Gail Williams. (1975) Method of examining RNA metabolism in cells in culture: Metabolism of vesicular stomatitis virus RNA. Journal of Virology 16: 1340-1344.